Project Summary PD/PI: Laura B. Duvall PhD Mosquitoes are obligate blood-feeders that pose increasing threats to global public health by spreading diseases, including Zika and malaria, among humans. Innate behaviors, including blood-feeding and mating, play key roles in vector biology and undergo dramatic changes influenced by environmental factors and internal state but we know little about the physiological changes underlying the behavioral readout. Our work focuses on understanding how neuropeptides regulate organismal physiology in mosquitoes. Specifically, how these peptides influence blood-feeding and utilization and post-mating responses. After a full meal of blood, female mosquitoes suppress their drive to bite humans for several days until they have matured and laid eggs. Behavioral suppression consists of several phases that are influenced by fluid regulation, nutrient sensing and satiety, and egg development. Although it is clear that these pathways influence each other, exactly how these individual components combine to produce the full expression of behavioral suppression remains unknown. We will use a combination of pharmacological and genetic techniques to ask how these pathways interact with each other on a signaling level as well as an anatomical level. Female mating responses are strongly regulated by peptide signals transferred from males to females. These signals prevent the female from accepting subsequent mates, ensuring the first male fathers all of her offspring, and allow her to allocate nutritional resources for reproduction. Using high-throughput cell-based screening techniques to pair ligands with receptors we will identify key receptors in the female that mediate post-mating responses and find small molecule drugs that act on them. We will map the anatomy that underlies post-mating responses using cutting-edge genetic techniques that enable us to label and manipulate the cells that express these receptors. These findings will increase our mechanistic understanding of how neuropeptide signaling acts on anatomical circuits to modulate chemosensory perception and motivated behavior. Additionally, these results will provide the basis for innovative approaches to mosquito control since receptors that affect mating and biting could be ?weaponized? against mosquitoes to disrupt these behaviors. Directly targeting behaviors that contribute to the spread of diseases offers an effective vector control solution by preventing transmission of all of the pathogens carried by these animals.